The population biological studies will be performed at both a theoretical and empirical level. Mathematical models for resource limited population growth and competition and for the interactions between bacteria and their viruses and conjugally transmitted plasmids will be developed. In the analysis of the properties of these models consideration will be given to the necessary and sufficient conditions for: 1) the establishment of virulent and temperate viruses and benign and bacteriocinogenic plasmids in populations of bacteria and 2) for the maintenance of stable regimes of co-existence between the bacteria and these infectious units. To test the reality of this theory, experiments will be performed with chemostat and serial transfer populations of E. coli and virulent virus of the T series, two temperate viruses, and three types of conjugally transmitted plasmids, an F' episome, an R factor and a colicinogenic factor. An experimental examination will be made of the relationship between protein variation and selection and the rates of base substitution mutation in E. coli. Three enzymes of known in vivo function are to be studied, beta-galactosidase, alkaline phosphate and one other which has not yet been chosen. Functional varients of these enzymes will be isolated and experiments will be performed to determine the relationship between their catalytic efficiency and the fitness of the alleles coding for their synthesis. Consideration will also be given to the conditions under which the regulation of these operons is selected for and against. Base substitution rates will be estimated from the rate of reversion from chain-terminating nonsense mutants. The primary concern of this investigation will be the relationship between the rates of this type of mutation and cell division.